In recent years, microfluidic “chip” technology has been widely applied for biochemical analysis1-3. In particular, various microfluidic chip techniques for cellular biochemical analysis have been recently developed4-19. For on-chip experiments, transport and selection of cells has been mainly achieved by liquid flow4-7, 9, 11, 20-22. The main technical issues for successful cell biochemical studies include methods of retaining the cell and maintaining cell integrity during reagent delivery. To date, the major methods for cell immobilization include (1) cell adhesion8, 23, 24, (2) physical retention within slit-type filters25-28, weir-type filters9, 11, 29, 30, or polymeric materials31, 32, and (3) dielectrophoresis33-35. Adhesion or blocking of the cell usually generates a local force on a small part of the cell's surface rather than uniformly on the whole cell surface. Even if these particle retention strategies do not have any negative effect on a stationary cell, the liquid flow which is essential for transport of buffer and reagents to the cell might damage the cell. This is because the liquid flow always exerts a force on the cell. Therefore, a strong flow might damage the cell. On the other hand, the flow should not be too weak to ensure a sufficient flow for reagent delivery. To balance the force of the liquid flow, an opposite force needs to be applied to the cell.
Recently, biochemical studies have benefited from microfluidic chip techniques1-3. In particular, studies have been conducted on biological cells retained within microfluidic chips4-19. Most studies have been performed on groups of cells, and only a few studies have been performed on single cells1, 6, 14, 19. Moreover, microfluidic chip single-cell experiments generally have been limited to only one type of stimulus, or the experiments are only conducted once or over short periods of time. This provides insufficient information regarding single-cell biochemistry. In many cases useful information regarding single cells is unattainable by measurements performed on an ensemble of cells. Although there is a need to study groups of cells (e.g. to understand cell-cell interactions), it is also useful to conduct genuine single-cell microfluidic experiments.